Substituted iminopyrrolidines



United States Patent 3,121,093 SUBSTITUTED HVIINOPYRROLIDINES Newman M. Bortnick, Greland, and Marian F. Fegley, Philadelphia, Pa, assignors to Robin 8: Haas Company, Philadelphia, Pa, a corporation of Delaware N0 Drawing. Filed Aug. 31, 1962, Ser. No. 220,884 8 Claims. (Cl. 260-313) This invention deals with specific substituted iminopyrrolidines as new compositions of matter. It further deals with a method for the preparation of these specific iminopyrrolidines.

The compounds of this invention may be represented by the formula The symbol R represents hydrocarbon groups of 1 to 10 carbon atoms, preferably aralkyl, cycloalkyl, aryl and alkaryl. The symbol R represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms. The symbols R and R may be a hydrogen atom or hydrocarbon groups containing from 1 to 10 carbon atoms, including alkyl, aralkyl, and cycloalkyl groups. In addition, R and R taken together with the carbon atoms to which they are joined may form a carbocyclic ring containing 5 to 6 carbon atoms which in turn may have alkyl substituents containing a total of no more than 4 additional carbon atoms. In addition, R and R taken together with the carbon atoms to which they are joined may form a carbocyclic ring containing 5 to 6 carbon atoms which in turn may have alkyl substituents containing a total of no more than four additional carbon atoms. In addition, R and R taken together with the carbon atom to which they are joined may form a carbocyclic ring containing 5 to 6 carbon atoms which in turn may have alkyl substituents containing a total of no more than 4 additional carbon atoms. The preferred embodiments are those in which R is phenyl, R is hydrogen, R is methyl and R is alkyl, and R may typically individually represent methyl, butyl, octyl, benzyl, phenylbutyl, cyclopentyl, cyclohexyl, and the like. R is typically phenylpropyl, cyclohexyl, phenyl, benzyl, butylphenyl, and the like.

Each of the symbols R and R represents a hydrogen atom, an alkenyl group of 3 to 18 carbon atoms, an aryl group of up to 10 carbon atoms, an alkarylalkyl group of up to 30 carbon atoms, an alkoxyalkyl group of 3 to 24 carbon atoms, a hydroxyalkyl group of 2 to 12 carbon atoms, and an alkylaminoalkyl group of 3 to 18 carbon atoms.

Typical R and R representations are hydrogen, cyclopentyl, cyclohexyl, butylcyclohexyl, octylcyclohexyl, butylcyclohexylethyl, propenyl, butenyl, hexenyl, octenyl, decenyl, dozlecenyl, octadecenyl, phenyl,naphthyl, methylphenyl, ethylphenyl, butylphenyl, octylphenyl, nonylphenyl, decylphenyl, hexadecylphenyl, octadecylphenyl, methylbenzyl, ethylbenzyl, butylbenzyl, octylbenzyl, dodecylbenzyl, butylphenylbutyl, octylphenylethyl, dioctylphenylethyl, dodecylphenyloctyl, methoxyethyl, methoxypropyl, methoxyhexyl, methoxydecyl, methoxyoctadecyl, ethoxyethyl, ethoxybutyl, ethoxyoctyl, ethoxydodecyl, propoxyethyl, propoxybutyl, propoxyheptyl, propoxytetradecyl, butoxyethyl, butoxybutyl, butoxyoctyl, butoxydodecyl, butoxyoctadecyl, pentoxyethyl, pentoxybutyl, pentoxydecyl, hexoxyethyl, hexoxyhexyl, hexoxydodecyl, hexoxyoctadecyl, heptoxyethyl, heptoxyoctyl, octoxyethyl, octoxybutyl, octoxyoctyl, octoxydodecyl, nonoxypropyl, nonoxyheptyl, nonoxytridecyl, dec- 3,121,693 Patented Feb. 11, 1954 34 E i [NR N (G) R R and (D) R R When R equals hydrogen, the compound represented by formula B is to varying degrees, according principally to the embodiments of R, R R R and R in tautomeric relationship, the compounds having the structures:

(E) [R2 IFS 4 Ii -l [NHR N/ and It is probable, based on the best experimental and analytical evidence, that the predominant tautomeric products are those of Formulas B and F, but appreciable amounts of E- are undoubtedly present. In the present sense, Formula B Will be referred to as the principal form of the three possible tautomeric structures (B, E, and F), but such a reference is meant to include the other two (E and F) tautorneric forms.

The symbol R represents hydrogen or an alkyl group of 1 to 9 carbon atoms, including cycloalkyl. The symbol X represents a hydroxyl group, an R 0 group in which R is lower alkyl, such as methyl, ethyl, isopropyl, or butyl, or an RNH group in which R has the same significance as previously set forth.

The above defined iminopyrroline and iminopyrrolidine reactants are prepared according to the method set forth in our copending applications, Serial Nos. 99,352 and 109,844, filed March 30, 1961, and May 15, 1961, respectively.

The present hydrogenation is carried out in the presence of a catalyst. Suitable as catalysts are Raney nickel, Raney cobalt, cobalt with ammonia, nickel with ammonia, cobalt-copper, nickel-cobalt, palladium, platinum, ruthenium, and the like. The catalyst may be employed in any convenient particle size. Generally, the smaller particle sizes produce the higher rates. If desired, the catalyst may be deposited on a carrier material in order to extend and activate it. Suitable for use as a carrier are activated alumina, activated clays, silica gel, charcoal, asbestos, pumice, and the like. Room temperatures and somewhat above may be employed when a noble metal is used as the catalyst. When the other materials are employed as catalyst, temperatures in the range of about 75 to 250 C. are employed with about 100 to 200 C. preferred. It is preferred that the hydrogenation be carried out at the lowest temperature at which reduction can occur within the ranges previously set out. An inert, volatile, organic solvent may be desirable, such as hydrocarbons, flcohols, others, and the like. The lower alkanols, such as methanol or ethanol, are particularly suited for this use. When the noble metals are used as catalysts, a small amount of an activating acid, such as acetic or hydrochloric, may be employed.

Pressures in the range of atmospheric to 10,009 p.s.i.g. are employed. Actually, higher pressures may be used if desired but in most instances, no apparent advantages are achieved for the extra effort extended. The reaction shown proceeds a little more rapidly at the higher pressures but lower pressures may be successfully employed with some of the catalysts, especially Raney nickel. The preferred range of pressures is atmospheric to 100 p.s.i.g. when noble metal catalysts are employed and 250 to 5000 p.s.i.g. when the transition metal catalysts are used.

The present reaction should be concluded as soon as one mole of hydrogen has reacted. Otherwise, if the reaction is conducted for periods of time that are substantially longer than that required for one mole of hydrogen to react, there is some chance that hydrogenolysis of the ring may occur. In some instances, this has been observed when the reaotion was conducted for prolonged periods of time. While no specific time limit in minutes or hours can be given, since actual times will vary with irninopyrroline or iminopyrrolidine reactants, catalysts,

temperatures, and pressures, it is emphasized that the reaction should be concluded after substantially one mole of hydrogen has reacted.

A preferred way of consumrn-ating the present reaction is to introduce the iminopyrroline or iminopyrrol-idine reactant along with a catalyst of the type described heretofore into a pressure retention reaction vessel and add hydrogen until a certain desired pressure is reached. The reaction vessel or at least the reaction ingredients may be preferably agitated such as by shaking or rotating until a precalculated drop in pressure is observed. This significant drop in pressure indicates that an equivalent amount of hydrogen has reacted. This precalculated pressure drop, indicating that an equivalent amount of hydrogen has reacted, is readily calculable by known methods. Therefore, an indication of reaction completion may be readily calculated and observed.

At the conclusion of the reaction, the product is obtained by filtering off the catalyst and shipping off the solvent. If desired, the products may be purified by distillation or recrystallization from hydrocarbons, ethers, or the like.

Typical compounds that may be hydrogenated according to the method of the present invention include -laurylimino-2amethyl-1-pyrroline, 2-methyl-5- aurylimino-Z-pyrroline, 1-lauryl-Z-imino-5-methylenepyrrolidine, 2,4-dihexyl-5-laurylirnino-4-methyl-2-pyrroline, 2,4-dihexyl-5-laurylimino-4-methyl-I-pyrroline, 3 hexyl-Z-imino-l-lauryl-3-methyl-5-hexylidenepyrrolidine, 4-methyl-2,4-diphenyl-51auryliminoQ-pyrroline,

2-laurylirnino-3, 3-pentamethylene-2,3,4,5,6,7hexahydroindole, 2,4,4-trimethyl-5-octadecylimino-2-pyrroline, 3, 3-dimethyl-2-iminol -ootadecyl-5-methylenepyrrolidine, 2, 3-dirnethyl-5-octadecylimino-Z-pyrroline, 2, 3-dimethyl-5-octadecylimino-1-pyrroline, 1-octadecyl-2-imino-4-methyl-5-methylenepyrrolidine, 4-methyl-2,4-dicycloheXyl-5-octadecylimino-Z-pyrroline, 3-cyclohexyl-2-imino-3 -methyl l -octadecy1-5-cyc1ohexylidenepyrrolidine, 5-octadecylimino-4-methyl-2,4-dicyclohexyll-pyrroline, Z-octadecylimino-Ia,3,6-trimethyl-2,3,4,5,6,7-hexahydroindole, Z-imino- 1-octadecy1-3, 3,6-trimetthyl-2,3,4,5 ,6,7-he1cahydroindole, 2,4,4-trimethyl-5-methylimino-2-pyrroline, 1-ethyl-2-imino-3,3-dimethyl-S-methylenepyrrolidine, 2,4,4-trimethyl-S-butylimino-2-pyrroline, l-butyl-Z-imino-B ,3dimethyl-5 -methylenepyrro1idine, 2,4,4-trimethyl-5-benzylimino-2-pyrroline, 1-benzyl-2-imino-3, 3-dimethyl-5 -methylenepy rrolidine, 2,4,4-trimethyl-5- 3-rnethoxypropylimino) -2-pyrrol-ine, 1- 3-methoxypropyl) -2-imino-3,S-dimethyl-S-methylenepyrrolidine, 2,4-dimethyl4-neopentyl-5- 3-diethylaminopropylimino -2-pyrroline, 1- 3-diethylaminopropyl) -2-irnino-3 -methyl-3 -neopentyl-S -methylenepyrrolidine, W 4-methy-l-4-ethyl-Z-propyl-S- (Z-methyl-2-hydroxypropylimino) -2-pyrroline, l- Z-methyl-Z-hydroxypropyl) -2-lmino3 -methyl-3-ethyl- 5-propylidenepyrrolidine, 2,4,4-trimethyl-5-phenylimino-2-pyrroline, 1-phenyl-2-imino-3,3-dimethyl-5 -methylenepyrrolidine, I 2,4,4-trimethyl-5-p-tolylirnino-2-pyrroline, 2-p-tolylimino-3,3-dimethyl-S-methylenepyrrolidine, 2-a-naphthylimino-3 ,3-pentamethylene-2,3,4,5,6,7-hexahydroindole, 2,4,4-trimethyl-2-hydroxy-S-benzyliminopyrrolidine, 2-hydroxy-2,4,4-trimethyl-S-methyliminopyrrolidine, 2-allyli-mino-3,3-pentamethylene-7a-hydroXy-2,3,3a,4,5,

6,7,7a-octahydroindole, 2-( 2-ethoxyethylimino) -7 a-hydroXy-3,3,6-trimethyl- 2,3,3 21,4,5,6,7,7a-octahydroindole, l-benzyl-5 benzylimino-2,4,4-trimethyl-2-pyrroline, 1-benzyl-2-benzylimino-3,3-dimethyl-5-methylenepyn rolidine, V 1-benzyl-5-b enzylimino-Z, 3-dimethyl-2-pyrroline, 1-benzyl-2-benzylimino-4-methyl-S-methylenepyrrolidine, 1-benzyl-5-benzylimino-2,4-diheXyl-4-methyl-2-pyrroline, l-benzyl-2 benzylimino-3 -hexyl-3-methyl-5-hexylidenepyrrolidine, 1-benzyl-5-benzylimino-2,4-bis Z-methylpropyl) -4-methyl-2-pyrroline, l-benzyl-2-benzylimino-3 -methyl-3- Z-methylpropyl 5-(2-methylpropylidene)-pyrrolidine, l benzyl-5-benzylimino-2,4-dimethyl-4- 2,2-dirnethylpropyl) -2-pyrroline, 1-benzyl-2-benzylimino-3 -meth-yl-3 (2, Z-dimethylprop yl) S-methylenepyrrolidine, 1-butyl-5-butylimino-2,4,4-trimethyl-Z-pyrroline, l-butyl-2-butylimino-3,3-dimethyl-S-methylenepyrrolidine, 1-butyl-imino-2-butyl-3-methyl- 1,4,5 ,6,7,7a-hexahydroisoindole, spiro{3,3 -dimethylbicyclo 2.2.1 )heptane-2,4[1'-butyl- 2 methyl-5 -butylimino-2-pyrroline] l-hutyl-2-butylimin0-3,3,6-trimethyl-2,3,4,5,6,7-hexahydroindole, l-dodecyl-5-dodecylimino-2,4,4-trimethyl-2-pyrroline, l-dodecyl-2-dodecylimino-3,3 -ditnethyl-5-methylenepyrrolidine, 1-p-tolyl-2-p-tolylimino-3,3 -pentamethylene-2, 3,4,5,

6,7-hexahydroindole,

1- (Z-butoxyethyl) -2- (Z-butoxyethylimino) -3 3 -p entamethylene-2,3,4,5,6,7-hexahydroindole,

1-( 3 -dimethylaminopropyl) -2- 3 -dimethylaminopropy imino) -3,3-pentamethylene-2,3,4,5,6,7-hexahydroindole,

l-hexadecyl-S-hexadecylimino-2,4-dimethyl-4- (2,2-dimethylpropyl -2 -pyrroline,

1-hexadecyl-2-hexadecylimino-3-methyl-3-(2,2-dimethylpropyl) -5-methylenepyrrolidine,

I-(Z-ethylaminoethyl) -5- 2-ethylaminoethylimino -2,4-

dimethyl-4- (2,2-dimethylpropyl) -2-pyrroline,

1- (Z-ethylaminoethyl) -2- (Z-ethylaminoethylimino) -3- me thyl-3- (2,2-dimethylpropyl) -5 -methylenepyrro1idine,

1( 2-phenylethyl -5- (Z-phenylethylimino) -2,4-.dimethyl- 4- (2,2-dimethylpropyl) -2-pyrroline,

1- 2-phenylethyl) -2- (phenylethylirnino) -3 -methyl-3- (2,2-dimethylpropyl)-5-methylenepyrrolidine, and

l-dodecyl-2-imino-3,3 dimethyl-S-methylenepyrrolidine.

Typical of the formula D reactants include S-methyl- S-hydroxy-Z-dodecylirninopyrrolidine, 3,3,5 trimethyI-S- hydroxy-2-benzyliminopyrrolidine, and 5-hydroxy-3,3,5- trimethyl-Z-phenylirninopyrrolidine, and the like. Other typical reactants include similar substituted pyrrolidines in which in place of the hydroxy group there may be employed methoxy, butoxy, amino, octylamino, anilino, benzylamino, dodecylbenzylam-ino, ethoxyethylamino, hydroxybutylamino, ethylaminoethylarnino, and the like.

The products that are thus obtained are stable, strong bases. Monilinia frllcticola and Stemphylium sarcinaeforme and give complete inhibition in concentrations of 0.1% and lower. They are particularly effective against Monilinia fructicola in concentrations as low as 0.005% when applied and evaluated according to standard test procedures. The present compounds, having a total of about 20 carbon atoms and more, are effective as extractants for the recovery of uranium from aqueous solutions of its ores. These products are valuable in this respect in that they form complexes with the acid H UO (SO that are soluble in kerosene, but insoluble in water. Thereby the uranium acid complex, as Well as many other acids also, may be selectively extracted from aqueous systems by kerosene solutions of these complexes.

The compounds of this invention have been presented in their free-base form and in this free-base form, they possess the valuable characteristics and concurrent utilities previously referred to. However, it is to be construed that the present invention includes the acid addition salts of these free-base products also. -It is desirable, in some instances, to employ the present products in their water-soluble salt form. For instance, in pesticidal applications, it is highly desirable to deal with watersoluble compounds in order that satisfactory spray solutions may be formulated. 'In other applications, wherein any physiological benefits are desired, it is frequently advantageous to employ the present products in their organic salt form in order to provide substantial neutrality with stability.

In order to prepare the salt forms of the present compounds, it is necessary only to react these compounds with a stoichiometric amount of the selected acid. The salt formation occurs readily at room temperature without the aid of a catalyst. If solid reactants are employed, it may be advantageous to use an inert volatile solvent such as benzene, toluene, xylene, hexane, heptane, methylene chloride, chloroform, or the like. The solvent can then be readily removed at the conclusion of the reaction by conventional methods. The salt product does not require any further purification although recrystallization from a solvent such as isooctane may be resorted to if a product of high purity is demanded.

While it is believed clear to one skilled in the art from the above description how the salts are prepared, such salt formation may be specifically illustrated by in- They are useful fungicides, particularly against dicating that one would take an equivalent amount of a selected compound of this invention in its free-base form and then add a stoichiometric amount of a selected acid which would, for instance, be 36.5 parts of hydrochloric acid, 98 par-ts of sulfuric acid, 60 parts of acetic acid, 72 parts of acrylic acid, and the like. The corresponding hydrochloric, sulfuric, acetic and acrylic acid salts respectively are readily formed. Similarly, other salt products may be prepared.

Typical organic and inorganic acids that may be employed are formic acid, acetic acid, propionic acid, butyric acid, caproic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, acrylic acid, methacrylic acid, crotonic acid, undecylenic acid, oleic acid, linoleic acid, linolenic acid, ricinoleic acid, propiolic acid, butynoic acid, cyclobutanecarboxylic acid, norcamphane-2-carbox ylic acid, benzoic acid, resorcyclic acid, oxalic acid, suc-. cinic acid, glutaric acid, adipic acid, sebacic acid, salicylic acid, maleic acid, fumaric acid, glutaconic acid, saccharic acid, dodecanedioic acid, octendioic acid, cyclohexaneacetic acid, cyclopentaneacetic acid, tridecanoic acid, hexynedioic acid, phthalic acid, cinnamic acid, benzenesulfonic acid, ethanesulfonic acid, naphthalenesulfonic acid, toluenesulfinic acid, glutarnic acid, glyoxalic acid, phenylglyoxalic acid, pyruvic acid, levulinic acid, glycine, aminocaproic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, carbonic acid, nitric acid, and phosphoric acid.

This application is a continuation-in-part of Serial No. 99,351, filed March 30, 1961, now abandoned.

The compounds of this invention, as well as the methods for their preparation, may be more fully understood from the following examples which are offered by way of illustration and not by way of limitation. Parts by Weight are used throughout.

Example 1 There are introduced into a reaction vessel 100 parts of 1-dodecyl-5-dodecylimino-2,4,4-trimethyl-2-pyrroline, 50 parts of methanol and 5 parts of Raney nickel. The vessel is pressurized with hydrogen at 1900 p.s.i.g. and the mixture is heated to to 145 C. At the end of 2%. hours, the vessel is cooled and vented. The reaction mixture is filtered and the precipitate is rinsed with methanol. The combined filtrates are fractionated under reduced pressure giving the product, l-dodecyl-2-dodecylimino-3,3,5-trirnethylpyrrolidine.

The same product is obtained by hydrogenating l-dO- decyl-2-dodecylin1ino-3,3-dimethyl 5 methylenepyrrolidine.

In a similar manner, there are produced l-butylimino- 2-butyl 3 methyl 1,3,3a,4,5,6,7,7a-octahydroisoindole, spiro{3,3 dimethylbicyclo(2.2.l)heptane 2,3'[l'-hutyl- 5-methyl-2-butyliminopyrrolidine]}, and l-butyl-Z-butylimino 3,3,6 trirnethyl-2,3,3a,4,5,6,7,7a-octahydroindole from 1-butylimino-2-butyl-3-methyl-1,4,5,6,7,7a-hexahydroisoindole, spiro{3,3-dimethylbicyclo(2.2.1)heptane-2, 4[1'-butyl-2'-methyl-5'-butylimino-2-pyrroline]} and 1- butyl-2-butylimino-3,3,6-trimethyl-2,3,4,5,6,7 hexahydroindole.

Example 2 There are added into a reaction vessel, 24 parts of 1-butyl-5-butylimino-2,4,4-trimethyl-2-pyrroline, 10 parts of methanol and 2 parts of Raney nickel. The reaction vessel is pressurized with hydrogen to 2000 p.s.i.g. and the temperature is increased to C. At the end of 1 /2 hours, the vessel is cooled and vented. The reaction mixture is distilled and two cuts of the product are obtained. The first cut boils at 259 to 262 C., and has an n value of 1.4680 and contains 75.73% carbon (75.56% theoretical), 12.81% hydrogen (12.68% theoretical), and 11.43% nitrogen (11.75% theoretical). The second cut boils at 263 to 266 C., has an n value of 1.4695 and contains 75.77% carbon (75.56% theoretical), 12.5% hydrogen (12.8% theoretical), and

11.71% nitrogen (11.75% theoretical). These cuts represent the product which is identified as l-butyl-Z-butylimino-3,3,S-trimethylpyrrolidine.

The same product is obtained by hydrogenating 1- butyl-2-butylimino-3,3-dimetl1yl-5-methylenepyrrolidine.

In a similar manner, there are prepared 1-benzyl-2- benZylimino-4,S-dimethylpyrrolidine, 1-butyl-2-butylimino-3,5 dihexyl-3-meth3.'lpyrrolidine, and 1-octyl-2-octylimino 3,5 dimethyl--(2,2 diniethylpropyl)pyrrolidine from 1-benzyl-5-benzylimino-2,3-dimethyl-2-pyrroline, 1- butyl-5-butylirnino-2,4-dihexyl-4-methyl-2-pyrroline and l-octyl-S-octylimino 2,4 dimethyl-4-(2,2 dimethylpropyl) -2-pyrroline respectively.

Example 3 There are introduced into a reaction vessel, 32.5 parts of 1-benzyl-5-benzylimino-2,4,4-trimethyl-2-pyrroline, 20 parts of methanol and 3 partsof Raney nickel. The vessel is pressurized with hydrogen to 1700 p.s.i. g. and the temperature increased to 148 to 152 C. At the end of two hours, the vessel is cooled and vented. The product is isolated by distillation at reduced pressure. The product boils at 176 to 184 C. at 0.25 mm. absolute pressure. It has an n value of 1.5702 and contains 9.05% nitrogen (9.14% theoretical). The product is identified as 1-benzyl-2-benzylimino-3,3,5-trimethylpyrrolidine.

The same product is obtained by hydrogenating 1- benzyl-Z-benzylirnino 3,3 dimethyl-5-methylenepyrrolidine.

In the same Way, there are prepared l-p-tolyl-2-p-tolylimino 3,3 pentarnethylene-Z,3,3a,4,5,6,7,7a-octahydroindole and 1-(Z-butoxyethyl)-2-(2-butoxyethylimino)-3, 3-pentamethylene-2,3,3a,4,5,6,7,7a-octahydroindole and 1- (3 dimethylaminopropyl)- 2 3 dimethylarninopropylimino) 3,3 pentamethylene-2,3,3a,4,5,6,7,7a-octahydroindole from l-p-tolyl-2-p-tolylin1ino-3,3-pentamethylene- 2,3,4,5,6,7 hexahydroindole, 1-(2-butoxyethyl)-2-(2-butoxyethylimino)-3,3-pentamethylene 2,3,4,5,6,7-hexahydroindole and 1-(3-dimethylaminopropyl)-2-(3-dimethylaminopropylimino)-3,3pentamethylene 2,3,4,5,6,7-hexahydroindole respectively.

In an analogous way, there are produced l-hexadecyl- 2-hexyldecylimino 3,5 dimethyl-3-(2,2-dimethylpropyl) pyrrolidine and I-(Z-phenylethyl)-2-(2-phenylethylimino) -'3 ,5 -dimethyl-3- 2,2-dimethylpropyl pyrrolidine from 1-hexadecyl-S-hexadecylimino 2,4 dimethyl 4 -(2,2-dimethylpropyl)-2-pyrroline and 1-(2-phenylethyl)-5-(2- phenylethylimino)-2,4-dimethyl'4- (2,2 dimethylpropyD- 2-pyrroline respectively.

Example 4 There are added to a reaction vessel 65 parts of 1- hydroxyethyl 5 hydroxyethylimino-2,4,4 -trimethy1-2- pyrroline, 50 parts of ethanol and 5 parts of Raney cobait. The vessel is pressurized With hydrogen at 2500 p.s.i.g. and the temperature is raised to 175 C. The reaction mixture is agitated and at the end of two hours, the reaction is complete. The vessel is cooled and vented and the contents of the vessel are filtered. The product is isolated by distillation under reduced pressure and is identified as 1-(2-hydroxyethyl) -2- (2-hydroxyethylimino)- 3,3,S-trimethylpyrrolidine.

Example 5 Methanol (25 parts), 2,4,4-trimethyl-5-dodecylimino-2 pyrroline (78 parts), and Raney nickel (3 parts) are charged to a hydrogenation bomb and pressun'zed with hydrogen (1775 p.s.i.g. at 20 C.). Hydrogen is absorbed as the temperature is raised above 50 C. and the hydrogenation is complete within two hours at which time the temperature has reached 150 C. The bomb is cooled, vented and opened. The contents of the bomb are filtered, the residual catalyst is Washed with methanol, and the combined filtrates are stripped of solvent and fractionated under reduced pressure. The product, 3,3,5- trimethyl 2 lauryliminopyrrolidine (67.4 parts86% yield), has a boiling point of 149154 C. at 0.4 mm. absolute pressure. The product contains 930% nitrogen (9.50% theoretical).

The same product is obtained by hydrogenating 2,4,4 trimethyl-S-dodecylimrino-1-pyrroline, 1-dodecyl-2,4,4-trimethylS-imino-Z-pyrroline, and 1-dodecyl-2-iniino-3,3- dimethyl-S-methylenepyrrolidine.

Both the solid and liquid forms of 2,4,4trin1ethyl5-do decylirnino-Z-pyr-roline give the same dodecyliminopyrrolidine on hydrogenation, as above, as supported by the identical infrared absorption spectra.

In the same manner, 2,4,4-trirnethyl-5-octadecylimino Z-pyrroline gives 3,3,5-trimethyl-Z-octadecyliminopyrrolidine; 2-methyl-S-dodecylimino-2-pyrroline gives S-methyl- 2-dodecyliminopyrrolidine; 2,4,4-trirnethyl-5-phenylimino- 2-pyrroline gives 3,3,5-trimethyl-2-phenyliminopyrroli dine; 4 methyl 2,4-di(2-methylpropyl)-5-benxylimino-2- pyrroline yields 3-methyl 3,5-di(Z-methylpropyl)-2-ben zyliminopyrrolidine; 2,3 dimethyl-5-ootylirnino-Z-pyrrm line results in 4,5-dimethyl-2-octyliminopyrrolidine; 3,3 pentamethylene-Z-butylhnino-2,3,4,5,6,7- hexahydroindole produces 3,3-pentamethylene-2-butylimino-2,3,3a,4,5,6,7,

7a octahydroindole; 3,3,5 trimethyl 2( 2 phenylethylimino) -2,3,4,5,6,7-hexahydroindole gives 3,3,5-trimethyl- 2- 2-phenylethylimino) -2,3, 3 21,4,5,6,7,7a-ootahydroindole; and 2,4-dimethyl-4-neopentyl-5-( 3-din1ethylaminopropylirnino)-2-pyrroline yields 3,5-diniethyl-3-neopentyl-2-(3- K 28 C. in an autoclave. Hydrogenation uptake begins at a C. and absorption of one mole of hydrogen per mole of substrate occurs at -150 C. The bomb is cooled and vented. The contents are filtered, the catalyst is washed with methanol and the combined filtrates are stripped and distilled under reduced pressure. The product which is collected in the range of 7294 C. at 0.5 mm. absolute pressure crystallizes on cooling. Recrystallization from heptane then from ethyl acetate gives the pure product having a melting point of 95.597 C.

Calculated for C H N 13.35% nitrogen, 13.45% (theoretical) The same product is obtained by hydrogenating 2,4,4- trimethyl-S-cyclohexylimino-l-pyrroline, 1-cyclohexyl-2,4,

4-trimethyl-5-imino 2 pyrroline, and 1 cyclohexyl 2- imino-3,3-dimethyl-S-methylenepyrrolidine.

In a similar Way, 3-methyl-1-cyclohexylimino-2,4,5,6, 7,7a-hexahydroisoindole gives 3 methyl 1 cyclohexylimino-2,3,3 a,4,5,6,7,7a-octahydroisoindole; 3,3,5-trimethyl-2- (Z-norc-amphanylmethylimino) 2,3 ,4,5, 6,7-hexahydroindole yields 3,3,5-trimethyl-2-(2 norcamphanylmethylimino) -2,3,3 a,4,5,6,7,7a-octahydroindole; 3,3apentamethylene-2-(3-butoxypropylimino)- 2,3,4,5,6,7 hexahydroindole gives 3,3-pentamethylene-2-(3-butoxypropylimino)- 2,3,3a,4,5,6,7,7a-octahydroindole; and 2,4,4-trimethyl-5- cyclohexylmethylimino-Z-pyrroline gives 3,3,5trimethyl- 2-cyclohexylmethyliminopyrrolidine.

Example 7 -It is not necessary to purify the iminopyrrolines before ature of 90 C. at 20 mm. absolute pressure. The residue and Raney nickel (20 parts) are charged to a hydrogenation autoclave and pressurized at 2180 p.s.i.g. at 29 C. Hydrogenation occurs during 7 hours at 145 160 C. The product boils at 132140 C. at 30 mm. absolute pressure. The product crystallizes on cooling and is obtained in 63% yield based on the starting ketonitrile.

Calculated for C11Hg2N2: total nitrogen 14.7%, titratable 7.7%. :Found: total nitrogen 14.7%, titratable 7.2%.

A higher boiling product, B.P. 157180 C. at 0.4 mm. absolute pressure (17% yield) is a dimeric product.

Calculated for C H N total nitrogen 15.4%, titratable 7.7%. Found: total nitrogen 14.8%, titratable 7.2%.

The slightly low nitrogen analysis observed in this experiment is due to the presence of a small amount of 1- butyl-3,3,S-trirnethyl-2-pyrrolidinone which is formed by hydrogenation of 1-b-utyl-2,4,4'trimethyl-2-pyrrolin-5-one which forms a side reaction product in the course of the preparation of the intermediate iminopyrroline. This side reaction is much less important when amines which boil above butylarnine are employed in the process. When cyclohexylarnine was substituted for butylarnine in the above process, the product which was obtained in 50% yield and which was identical with that produced in Example 6, above, had total nitrogen and titratable nitrogen analyses which matched the theoretical values within experimental error.

In an entirely similar manner, 2-methyl-2,4-diphenyl-4- oxobutauenitrile is condensed with octylamine and hydrogenated without isolation to give 3-rnethyl-3,5-diphenyl- 2-octyliminopyrrolidine; 4-oxopentanenitrile and octadecylamine followed by hydrogenation give 5-methyl-2-octadecyliminopyrrolidine; and 2,2-dimethyl-4-oxopentanenitrile and benzylamine followed by hydrogenation give 3,3,5-trimethyl 2 benzyliminopyrrolidine. Similarly, 3- methyl-4-oxopentanenitrile and decylarnine followed by hydrogenation give 4,5-dimethyl-Z-decyliminopyrrolidine and 2,2-dimethyl-4-oxopentanenitrile and 2-norcamphanylmethylarnine followed by hydrogenation give 3,3,5-tri methyl-2-(2-norcamphanyhnethylirnino)pyrrolidine. The process of Example 7 provides the most straightforward method for the direct preparation of the irninopyrrolidines from the parent gamma-ketonitriles.

Example 8 For the preparation of iminopyrrolidines in which R is H, methyl, ethyl, propyl or isopropyl, the azeotropic procedure described in Example 7 is not feasible. The following procedure has been used successfully in such cases. Anhydrous methylamine (58 parts), 2,2-dimethyl- 4-oxopentanenitrile (63 parts), and Raney nickel (5 parts) are charged to a Dry-Ice-cooled autoclave. The autoclave is sealed and left standing for 72 hours. The bomb is then placed in a shaker and charged with hydrogen at 1920 p.s.i.g. at 32 C. Hydrogenation is complete after 1.5 hours at 1l2l41 C. The autoclave is cooled, vented, and opened. The contents are filtered and the catalyst residue rinsed with ether. Removal of the solvent gives a crystalline product which is recrystallized first from ether then from heptane to give the analytical sample having a melting point of 102-l08 C.

Calculated for C H N total nitrogen 20.0% titratable 10.0%. Found: total nitrogen 19.6%, titratable 9.5%. The yield is 82%.

In a similar manner, ethylamine and 2,2-dirnethyl-4- oxopentanenitrile give 3,3,S-trirnethyl-Z-ethyliminopyrrolidine; methylarnine and 2-(l-cyanocyclohexyl)-cyclohexanone give 3,3-pentarnethylene-Z-methylimino-Z,3,3a,4,5,6, 7,7a,-octahydroindole; and propylamine and 2-(1-cyanol-rnethylethyl) 5 methylcyclohexanone yield 3,3,6-trimethyl-2-propylirnino2,3,3a,4,5,6,7,7a-octahydroindole.

l 0 Example 9 The procedure of Example 8 is repeated substituting anhydrous ammonia for methylamine. The products are distilled to give the product (25 parts), having a boiling point of 104115 C. at 1.0 mm., absolute pressure. The product solidified "m the receiver. Titration of a sample showed that it is a mixture of the desired product, 3,3,5- trimethyl-2-iminopyrrolidine and 3,3,5-trimethyl-2-pyrroli dinone of which the desired product, the former, comprises approximately The product is dissolved in aqueous 14% hydrochloric acid solution and the aqueous solution is extracted four times with diethyl ether. The aqueous solution is then stripped of ether, water, and free hydrogen chloride, under reduced pressure. The glassy hydrochloride finally crystallized after washing several times with ether. The solid is dissolved in methanolic sodium hydroxide solution. The product boils at C. at 1.1 mm. absolute pressure and upon recrystallization from heptane gives the analytical sample, having a melting point of 103 104.5 C.

Calculated for C7H14N2I 22.2% nitrogen, N neutral equivalent, 127. Found: 22.2% nitrogen, neutral equivalent, 127.

Example 10 Methanol (50 parts), 3,3,S-trirnethyl-S-hydroxy-2-rnethyliminopyrrolidine (78 parts), and Raney nickel (5 parts) are charged to a hydrogenation bomb. The bomb is pres surized with hydrogen and reduction occurs at 50150 C. over a period of three hours. The reaction mixture is stripped of solvent and distilled under reduced pressure. The distillate crystallizes and has the same physical constants as those reported in Example 8. In a similar fashion, 3,3,S-trimethyl-5-methylamino-2-rnethyliminopyrrolidine (92 parts), methanol (50 parts), and Raney nickel (5 parts) are hydrogenated at 10002000 p.s.i.g. at 60- to give the same product in 78% yield. In a similar way, 3,3-pentamethylene-7a-hydroxy-Z-rnethylirnino- 2,3,3a,4-,5,6,7,7a-octahydroindole gives 3,3-pentamethylene-2-methylimino-2,3,3a,4,5,6,7,7a-octahydroindole; 5,5, 7-trimethyl-7a-hydroxy 2 methylimino-2,3,3 a,4,5,6,7,7aoctahydroindole yield 5,5,7-trimethyl-2-methylimino-Z,3, 3a,4,5,6,7,7a-octahydroindole; 4,5-dimethy1 5 methylamino-2-methyliminopyrrolidine produces 4,5-dimethyl-2- methyliminopyrrolidine; and 3,5-dimethyl-3-neopentyl-5- methylamino-Z-methyliminopyrrolidine gives 3,5dimethyl- 3-ueopentyl-2-methylirninopyrrolidine.

Example 11 Methanol (50 parts), 3,3,5-trimethyl-S-methoxy-Z-methylirninopyrrolidine (43 parts), and Raney nickel (3 parts) are charged to a hydrogenation autoclave which is then pressurized with hydrogen at 1850 p.s.i.g. at 30 C. Hydrogenation occurs during 1.5 hours at 50 120 C. The autoclave is cooled and vented. The contents are filtered. The filtrate is stripped of solvent and the residue is distilled under reduced pressure to give the product of 'Example 8.

In a similar fashion, 3,3,S-trimethyl-5-rnethoxy-2-benzyliminopyrrolidine gives 3,3,5 trimethyl 2 benzyli minopyrrolidine; 3,3-pentamethylene-7a-methoxy-2-dodecylirnino-2,3,3a,4,5,6,7,7a-octahydroindole produces 3,3- pentamethylene-Z-dodecylimino 2,3,3a,4,5,6,7,7a octahydroindole; and 3-methyl-3-methoxy-l-cyclohexylimino- 2,3,321,4,5,6,7,7a-octahydroisoindole gives 3-methyl-1-cyclohexylirnino-2,3,3a,4,5,6,7,7a-octahydroisoindole.

Example 12 To a solution of 3,3,S-trimethyl-Z-butyliminopyrrolidine (18.2 parts) dissolved in aqueous 10% hydrochloric acid solution (25 parts) is added a solution of sodium nitrite (7.5 parts) in water (25 parts). The addition requires 20 minutes and the temperature is maintained at 20 25 C. during this period. The mixture is allowed to stand at room temperature overnight and is homogeneous the l 1 following morning. The mixture is extracted with ether (100 parts) in four portions. Evaporation of the ether gives substantially no residue. Treatment of the aqueous solution with aqueous sodium hydroxide solution (50 parts) and extraction with ether (100 parts) in four portions gives the starting material, 3,3,5-trirnethyl-2- butyliminopyrrolidine, in 82% recovery. Thus, no reac tion has occurred. Had the starting material had the structure, 3,3,S-trimethyl-1-butyl-Z-iminopyrrolidine, easy reactions with nitrous acid should have occurred and the reaction product isolated should have been 3,3,5-trimethyl- 1-butyl-2-pyrrolidinone, a neutral product. This establishes that the exocyclic imino nitrogen atom bears an alkyl group rather than a hydrogen atom. Comparison of the infrared absorption spectrum of this material with that of a compound in which the exocyclic imino nitrogen atom bears hydrogen shows very marked differences which likewise supports the structure stated for this material.

Boiling for one hour with either aqueous 10% hydrochloric acid or aqueous 10% potassium hydroxide gave only recovered starting material.

When 3,3,5-trimethyl-Z-butyliminopyrrolidine is boiled with excess aqueous potassium hydroxide for 24 hours, n-butylamine (75% yield) is isolated in the distillate. The aqueous solution is neutralized with concentrated hydrochloric acid, evaporated to dryness, and extracted with alcohol. The alcohol is removed and the residue is distilled under reduced pressure. The distillate crystallized and is recrystallized from heptane to give a 51% yield of 3,3,5-trimethyl-2-pyrrolidinone, melting point and mixed melting point with a known sample, 91-92 C.

Example 13 Hydrogen (.09 mole) is absorbed when the solid 5- dodecylimino 2,4,4 trimethylpyrroline, 29.2 parts (.1 mole), in ethanol solution (100 ml.) in the presence of rhodium on alumina, 2 parts, is charged to the Adams apparatus under 40 lbs. p.s.i.g. of hydrogen. The catalyst is separated by filtration and 32.5 parts of crude product remains after the ethanol is removed by stripping under reduced pressure. A first crop of solid product ('M.P. 83 84 C.) separates when the material is recrystallized from benzene and heptane. A second crop melts below 78- 79 C. Examiantion of the infrared spectrum indicates that hydrogenation has occurred. The yield (based on crude product) is substantially quantitative.

Crude liquid, l-dodecyl-S-imino-Z,4,4-trimethyl-2-pyrroline, 50 parts (0.17 mole), in ethanol (100 m1.) over rhodium on alumina, 5 parts, under hydrogen at 700 p.s.i.g. absorbs hydrogen during five hours at room temperature (28 C.). The filtered reaction mixture is stripped on the Rinco evaporator. The residue, 49 parts, which did not crystallize, is distilled. The following fractions are collected:

Pot Weight, Neutral Melting Temp. g. Equiv- Point,

alent C.

(a) 94-131 (L/.20 mm 133156 3.3 238.5 (b) 131 G./0.20 mn1.-144

I 12 salts from l he hydrogenation rather than l-alkyl-Zdmino- S-methylpyrrolidine. However, as shown in this example, it is possible to avoid this isomerization, such as by con ducting the reaction at milder temperatures.

Example 14 2-dodecylirnino-3,3,5-trimethylpyrrolidine, 5 parts (.02 mole), is heated at reflux for 9 hours with a solution of potassium hydroxide, 3 parts, in ethylene glycol (21 ml.). Nitrogen is used to flush any gases which might be evolved through 3.6 N hydrochloric acid. No ammonia is evolved. The oil layer is separated and distilled to give: 65 C./0'.2 Inm.92 C./.3 mm., 2.7 parts.

The infrared spectrum shows the presence of free.

laurylamine. This is confirmed by preparation of the ch10- mplatinate (C l-I NH .HCl) PtCl Calculated for C H FtCI carbon 36.92%, hydrogen 7.23%, platinum as ash 25.08%. Found: carbon 36.95%, hydrogen 7.26%, platinum as ash 25.24%.

A second component is 3,3,5-trirnethyl-Z-pyrrclidinone. It is isolated from the aqueous filtrate after laurylamine hydrochloride precipitates when dilute hydrochloric acid is added.

Similar results are obtained on hydrolysis of material obtained by hydrogenation in the presence of Raney nickel.

Example 15 Hydrolysis of 1-dodecyl-2-imino-3,3,5-trimethylpyrrolidine, 5.7 parts (0.02 mole), by a solution of potassium hydroxide, 3 parts, in ethylene glycol (21 ml.) is incomplete after 9 hours at reflux temperature 165 167 C. Titration of the hydrochloric acid solution through which the vent gases are fiushed shows that ammonia is liberated.

The neutral equivalent of the oil layer of the reaction mix- 7 ture is 1000 just before the reaction is stopped. This corresponds to about 70% hydrolysis if all of the hydrolysis gives ammonia, which is liberated as it forms. The remaining oil layer is separated and distilled. The following fractions are collected:

(a) 142 C./.3 mrn .35 (b) 142149 C./.3 mm 2.0 (C) 149-165 C./.3 mm 0.5 Residue .5

The infrared spectrum of fraction b shows that it is and the acid addition salts thereof, in which R and R are each members selected from the class consisting of hydrogen, cycloalkyl and alkylcycloalky-l groups of up to 18 carbon atoms, alkenyl of 3 to 18 carbon atoms, phenyl, naphthyl, allcoxyalkyl groups of 3 to 24 carbon atoms, hydroxyalkyl groups of 2 to 12 carbon atoms, and alkylaminoalkyl groups of 3 to 18 carbon atoms, R taken individually represents a member selected from the class consisting of phenylalkyl, cycloalkyl, phenyl, naphthyl, and alkylphenyl groups of up to 10 carbon atoms, R taken individually represents a member selected from the class consisting of hydrogen and alkyl groups of 1 to 4 carbon atoms, R and R taken individually represent members selected from the class consisting of hydrogen, and a hydrocarbon group or" 1 to 10 carbon atoms selected from the class consisting of all-tyl, cycloalkyl, and phenylalkyl, R and R taken collectively with the carbon atoms to which they are joined form a carbocyciic ring of 5 to 6 carbon atoms free of aromatic unsaturation including alkyl substituents of a total of no more than 4 additional carbon atoms, R and R taken collectively with the carbon atoms to which they are joined form a carbocyclic ring of to 6 carbon atoms free of aromatic unsaturation including alkyl substituents of a total of no more than 4 additional carbon atoms, and R and R taken collectively with me carbon atoms to which they are joined form a carbocyclic ring of 5 to 6 carbon atoms free of aromatic unsaturation including alkyl substituents of a total of no more than 4 additional carbon atoms.

2. The compound, 2cycloheXy1imino-3,3,5-trimethylpyrrolicline.

3. The compound, 1-butylimino-2-butyl-3-methyl-1,3, 3a,4,5,6,7,7a-octahydroisoindole.

4. The compound, spiro{3,3-dimethylbicyclo(2.2.1)- heptane 2,3'[1' butyl-S'-methyl-Z'-butyliminopyrrolidine1}.

5. The compound, 1-butyl-2-butylimino-3,3,6-trimethyl- 2,3,3a,4,5,6,7,7a-octahydroindole.

6. The compound, 3,3-pentamethylene-Z-butylimino- 2,3,321,4,5,6,7,7a-octahydroindole.

7. A method for the preparation of a compound having the formula which comprises reacting with hydrogen in the temperature range of about 25 to 250 C. in the presence of a hydrogenation catalyst, a member from the class consisting of a compound having the formulas 3,; E i YR in which R and R are each members selected from the class consisting of hydrogen, cycloalkyl and alkylcycloalkyl groups of up to 18 carbon atoms, alkenyl of 3 to 18 carbon atoms, phenyl, naphthyl, alkoxyalkyl groups of 3 to 24 carbon atoms, hydroxyalkyl groups of 2 to 12 carbon atoms, and alkylaminoallryl groups of 3 to 18 carbon atoms, R taken individually represents a member selected from the class consisting of phenylalkyl, cycloalkyl, phenyl, naphthyl, and alkylphenyl groups of up to 10 carbon atoms, R taken individually represents a member selected 'from the class consisting of hydrogen and alkyl groups of 1 to 4 carbon atoms, R and R taken individually represent members selected from the class consisting of hydrogen, and a hydrocarbon group of 1 to 10 carbon atoms selected from the class consisting of alkyl, cycloalkyl, and phenylalkyl, R and R taken collectively with the carbon atoms to which they are joined from a carbocyclic ring of 5 to 6 carbon atoms free of aromatic unsaturation including alkyl substituents of a total of no more than 4 additional carbon atoms, R and R taken collectively with the carbon atoms to which they are joined form a carbocyclic ring of 5 to 6 carbon atoms free of aromatic unsaturation including alkyl substituents of a total of no more than 4 additional carbon atoms, and R and R taken collectively with the carbon atoms to which they are joined form a carbocyclic ring of 5 to 6 carbon atoms free of aromatic unsaturation including alkyl substituents of a total of no more than 4 additional carbon atoms, R is a member from the class consisting of hydrogen and an alkyl group of 1 to 9 carbon atoms, and X is a member from the class consisting of a hydroxyl group, and RNH group, and an R 0 group in which R is lower alkyl.

8. A method according" to claim 7, in which the reaction is conducted in the temperature range of about to 200 C. in the presence of an inert, volatile, organic solvent, and at pressures up to about 10,000 p.s.-i.g.

Buckley: 1. Chem. Soc., pages 1508-1511 (1947). G-ittos: J. Chem. Soc., pages 23712376 (1955). 

1. A MEMBER SELECTED FROM THE CLASS CONSISTING OF THE COMPOUND OF THE FORMULA
 2. THE COMPOUND, 2-CYCLOHEXYLIMINO-3,3,5-TRIMETHYLPYRROLIDINE. 